Safety and efficacy of rituximab in systemic sclerosis (DESIRES): a double-blind, investigator-initiated, randomised, placebo-controlled trial.
Journal
The Lancet. Rheumatology
ISSN: 2665-9913
Titre abrégé: Lancet Rheumatol
Pays: England
ID NLM: 101765308
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
02
02
2021
revised:
12
03
2021
accepted:
17
03
2021
medline:
1
7
2021
pubmed:
1
7
2021
entrez:
27
1
2024
Statut:
ppublish
Résumé
Systemic sclerosis is a connective tissue disease characterised by multiorgan fibrosis with an autoimmune background and poor prognosis. Although a few drugs have shown some efficacy in treating the disease, there remains a great unmet medical need. We aimed to investigate the efficacy and safety of rituximab in patients with systemic sclerosis. We did a double-blind, investigator-initiated, randomised, placebo-controlled trial at four hospitals in Japan. Patients aged 20-79 years, who fulfilled the 2013 American College of Rheumatology and European League Against Rheumatism classification criteria for systemic sclerosis, with a modified Rodnan Skin Score (mRSS) of 10 or greater, and an expected survival of at least 6 months were randomly assigned (1:1) to receive intravenous rituximab (375 mg/m Between Nov 28, 2017, and Nov 6, 2018, 80 individuals were screened and 56 (70%) were enrolled and randomly assigned; 51 (91%) were women and five (9%) were men. 27 (96%) of 28 patients in the rituximab group and 22 (79%) of 28 patients in the placebo group received at least one dose of their allocated treatment and completed 24 weeks of follow-up. The absolute change in mRSS 24 weeks after initiation of study treatment was lower in the rituximab group than in the placebo group (-6·30 in the rituximab group vs 2·14 in the placebo group; difference -8·44 [95% CI -11·00 to -5·88]; p<0·0001). Adverse events were similar in both groups and occurred in 28 (100%) of 28 patients in the rituximab group and 23 (88%) of 26 patients in the placebo group. One serious adverse event leading to treatment discontinuation occurred in one patient in each group (decreased serum albumin in the rituximab group and biliary enzyme increase in the placebo group). The most common adverse event was upper respiratory infection, which occurred in 11 patients (39%) in the rituximab group and ten patients (38%) in the placebo group. There were no deaths during follow-up. Rituximab appears to be an effective and safe treatment for systemic sclerosis. Although this study has some limitations, this is the first clinical trial to show efficacy of rituximab with skin sclerosis as the primary endpoint. Japan Agency for Medical Research and Development (AMED), Zenyaku Kogyo. For the Japanese translation of the abstract see Supplementary Materials section.
Sections du résumé
BACKGROUND
BACKGROUND
Systemic sclerosis is a connective tissue disease characterised by multiorgan fibrosis with an autoimmune background and poor prognosis. Although a few drugs have shown some efficacy in treating the disease, there remains a great unmet medical need. We aimed to investigate the efficacy and safety of rituximab in patients with systemic sclerosis.
METHODS
METHODS
We did a double-blind, investigator-initiated, randomised, placebo-controlled trial at four hospitals in Japan. Patients aged 20-79 years, who fulfilled the 2013 American College of Rheumatology and European League Against Rheumatism classification criteria for systemic sclerosis, with a modified Rodnan Skin Score (mRSS) of 10 or greater, and an expected survival of at least 6 months were randomly assigned (1:1) to receive intravenous rituximab (375 mg/m
FINDINGS
RESULTS
Between Nov 28, 2017, and Nov 6, 2018, 80 individuals were screened and 56 (70%) were enrolled and randomly assigned; 51 (91%) were women and five (9%) were men. 27 (96%) of 28 patients in the rituximab group and 22 (79%) of 28 patients in the placebo group received at least one dose of their allocated treatment and completed 24 weeks of follow-up. The absolute change in mRSS 24 weeks after initiation of study treatment was lower in the rituximab group than in the placebo group (-6·30 in the rituximab group vs 2·14 in the placebo group; difference -8·44 [95% CI -11·00 to -5·88]; p<0·0001). Adverse events were similar in both groups and occurred in 28 (100%) of 28 patients in the rituximab group and 23 (88%) of 26 patients in the placebo group. One serious adverse event leading to treatment discontinuation occurred in one patient in each group (decreased serum albumin in the rituximab group and biliary enzyme increase in the placebo group). The most common adverse event was upper respiratory infection, which occurred in 11 patients (39%) in the rituximab group and ten patients (38%) in the placebo group. There were no deaths during follow-up.
INTERPRETATION
CONCLUSIONS
Rituximab appears to be an effective and safe treatment for systemic sclerosis. Although this study has some limitations, this is the first clinical trial to show efficacy of rituximab with skin sclerosis as the primary endpoint.
FUNDING
BACKGROUND
Japan Agency for Medical Research and Development (AMED), Zenyaku Kogyo.
TRANSLATION
UNASSIGNED
For the Japanese translation of the abstract see Supplementary Materials section.
Identifiants
pubmed: 38279402
pii: S2665-9913(21)00107-7
doi: 10.1016/S2665-9913(21)00107-7
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT04274257']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e489-e497Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests We declare no competing interests.